People with Parkinson's disease often develop autonomic dysfunctions including those in the lower urinary tract (urinary bladder and urethra). The common type of bladder complication is hyperactive bladder that induces frequent voiding and urinary incontinence. Parkinson's disease also affects urethral sphincter function to deter its relaxation when patients start voiding, resulting in voiding difficulty. The high incidence (50-70%) of lower urinary tract dysfunction in Parkinson's disease has been reported. These urological symptoms greatly affect the quality of life for patients, caregivers and families. However, these urological problems have often been ignored and the pathophysiology for lower urinary tract dysfunction in Parkinson's disease is not fully understood. We therefore propose a research project to investigate the dopaminergic and other transmitter mechanisms inducing bladder and urethral dysfunctions in Parkinson's Disease. It has been documented that hyperactive bladder in Parkinson's disease is in part induced by a loss of activation of central D I -like dopamine receptors following the degeneration of dopaminergic neurons in the substantia nigra, whereas the lack of D2-like dopamine receptor activation primarily contributes to locomotor dysfunctions in Parkinson's disease. An activation of dopamine D2 receptors, which is a major target in the treatment of motor dysfunctions in Parkinson's disease, exacerbates urinary frequency since D2 receptor agonists facilitate the micturition reflex. Thus, it is likely that autonomic dysfunction in the lower urinary tract is induced by the mechanisms different from those inducing motor dysfunction in Parkinson's disease. However, the detailed mechanisms and sites of action for dopaminergic control of bladder function in the central nervous system have not been fully elucidated. Moreover, dopaminergic mechanisms controlling urethral function has never been investigated under either normal or pathological conditions such as Parkinson's disease. Thus, this research project will examine if specific sites of action and receptor subtype specificity in dopaminergic and other transmitter pathways controlling bladder and urethral function using a rodent model of Parkinson's disease induced by 6-hydroxydopamine-induced lesions of the nigrostriatal pathway. By defining the pathophysiology of lower urinary tract dysfunction in Parkinson's disease, we can offer the hope of prevention, reversal, and even cure of urologic dysfunction in Parkinson's disease. This is a high priority in the urologic care of patients with Parkinson's disease.